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. 2022 Aug;82(5):436-446.
doi: 10.1002/jdn.10200. Epub 2022 Jul 5.

An investigation of the effects of chronic zonisamide, sultiam, lacosamide, clobazam, and rufinamide anti-seizure medications on foliculogenesis in ovarian tissue in prepubertal non-epileptic rats

Pınar Özkan Kart  1 , Seren Gülşen Gürgen  2 , Gülnur Esenülkü  1 , Beril Dilber  1 , Nihal Yıldız  1 , Uğur Yazar  3 , Hayrunnisa Yeşil Sarsmaz  2 , Ali Samet Topsakal  3 , Tülay Kamaşak  1 , Elif Acar Arslan  1 , Sevim Şahin  1 , Ali Cansu  1
Affiliations

An investigation of the effects of chronic zonisamide, sultiam, lacosamide, clobazam, and rufinamide anti-seizure medications on foliculogenesis in ovarian tissue in prepubertal non-epileptic rats

Pınar Özkan Kart et al. Int J Dev Neurosci. 2022 Aug.

Abstract

We aimed to determine the morphological and histological effects of zonisamide, sultiam, lacosamide, clobazam, and rufinamide on ovarian folliculogenesis in rats. Sixty female Wistar rats were divided into six experimental groups as control, zonisamide, sultiam, lacosamide, clobazam, and rufinamide groups; control solution and drugs were administered by gavage for 90 days. The number of healthy follicles in the control group was significantly higher than in the anti-medication groups (p < 0.001), and the number of corpus luteum was significantly lower (p < 0.001). There was a significant difference in the number of TUNEL positive apoptotic follicles between the control and drug groups (p < 0.001). With EGF, IGF-1, and GDF-9 staining, a very strong immunoreaction was observed in the ovarian multilaminar primary follicle granulosa cells and oocytes in the control group compared to the drug group (p < 0.001). Long-term anti-seizure medication with zonisamide, sultiam, lacosamide, clobazam, and rufinamide from prepubertal to adulthood causes apoptosis and disruption of folliculogenesis in the ovarian follicles of nonepileptic rats.

Keywords: EGF; GDF-9; IGF-1; anti-seizures medication; apoptosis; epilepsy; ovary.

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